Molecular Genetics of Complex Diseases and Phenotype

Our research program on genetic variation including human molecular genetics deals with genetic and epigenetic factors associated with complex diseases and phenotypes. During the pre-recombinant DNA era, the level of investigation relied on chromosomes and protein polymorphism. We recognized the significance of this technology and acquired it for our research.

Besides changing the level of investigation in our research, we launched Molecular Genetic Diagnosis Laboratory under Child Health Research Institute (with Dr. M. Coulter-Mackie), currently located in LHSC. It also allowed us to develop the Molecular Genetics Unit, currently the main site of molecular studies in the Faculty of Science.

As expected, these technologies have shifted our research to the level of DNA and RNA using the most modern genome-wide approaches. On reflection, this shift was essential, as most of the common and complex disorders, the focus of our research, had evaded identification of causal genes and mutations by traditional methods. It was also essential if we wished to make use of the complete human, mouse and other genome sequences being produced through genome sequencing projects. Needless to say, to day we are able to pursue novel approaches (positional candidate genes), hypotheses (epi-mutation) and whole genome based methods (microarrays; expressed, SNPs and methylation specific oligonucleotide microarrays). More important, this timely development has allowed a successful transition of our research; from a single gene paradigm to the complete genome. We have argued that this change in the paradigm is critical in studies on the complex disorders, particularly involving the brain. In this context, our focus on neurogenomics in a novel way by combing epigenetic and genetic features using high throughput genomic methods including Bioinformatics is internationally recognized by its regular publications, international meeting invitations discussing novel results.

Our neurogenomics studies are being undertaken with focus on Schizophrenia, Narcolepsy, Alcoholism, Fetal Alcohol Syndrome and Cancers. They involve human families including monozygotic twins discordant for the disease and mouse as the genetic animal model. Additionally, we make use of rare patients and families (eg. patients with 22q11 deletions and schizophrenia) in such studies, through our collaboration with researchers in neuroscience and Psychiatry (Dr. R.O'Reilly). The results obtained have offered a novel insight, particularly the importance of epigenetics and gene regulation, in the dissection of most complex features including behaviors. This novelty is recognized by the genetics community including granting agencies (NSERC, NAMI (NIH), CIHR, ATCG, OMHF, SSO, etc.) who have funded this research program fully and adequately for over 25 years.

No story of our research will be complete without a large number of very bright and dedicated people associated with it over 25 years. The unique feature of our research is that almost all of these trainees are now practicing genetics at different levels; as physician, professor, lawyer, genetic counselors, research technicians/associates, teachers and administrators just to name a few. Our trainees have taken novel ideas and approaches internationally as independent researchers. There is no better reward than this.